Microcystin-LR (MC-LR) is a widely known hepatotoxin which could induce the occurrence and metastasis of hepatocellular carcinoma. In recent years, with the frequent outbreak of cyanobacteria, the harm of MC-LR has gradually attracted more attention. Hence, this study focused on the effect of MC-LR on DNA damage in HepG2 cells, identifying the types and sources of free radicals that make an important function on this issue. Our data suggested that MC-LR induced concentration- and time-dependent increasement of DNA double-strand breaks (DSBs). After exposure to 1 μM MC-LR for 3 days, the protein expression and immunofluorescence staining of γ-H2AX was significantly increased. Using a scavenger of mitochondrial O₂^.- (4-hydroxy-tempo), a inhibitor of mitochondrial NOS (7-nitroindazole), and a scavenger of ONOO⁻ (uric acid), it was revealed that ONOO⁻ originated from mitochondria made a significant contribution to the genotoxicity of MC-LR. Moreover, a significant decreasement of mitochondrial membrane potential (MMP) was observed. These findings suggested that peroxynitrite targeting mitochondria plays a vital role in the MC-LR-induced genotoxic response in mammalian cells.

微囊藻毒素-LR（MC-LR）是一种广为人知的肝毒素，可诱导肝细胞癌的发生和转移。近年来，随着蓝细菌的频繁爆发，MC-LR的危害逐渐引起人们的关注。因此，本研究集中于MC-LR对HepG2细胞DNA损伤的影响，确定了在此问题上起重要作用的自由基的类型和来源。我们的数据表明，MC-LR诱导DNA双链断裂（DSBs）的浓度和时间依赖性增加。暴露于1μMMC-LR 3天后，γ-H2AX的蛋白质表达和免疫荧光染色显着增加。使用线粒体O ₂ ^.-的清除剂（4-羟基-TEMPO），线粒体NOS（7-硝基吲唑）的抑制剂，和ONOO的清除剂^- （尿酸），据透露，ONOO ^-源自线粒体制成MC-LR的遗传毒性一个显著贡献。此外，观察到线粒体膜电位（MMP）的显着降低。这些发现表明，过氧亚硝酸盐靶向线粒体在哺乳动物细胞中MC-LR诱导的遗传毒性反应中起着至关重要的作用。